Transcript Hypersensitivity Reactions

Hypersensitivity
Reactions
Injurious, patologic immune reactions causing
tissue injury and disease
Excessive or aberrant immune response to:
Foreign antigens (non-self)
- non-infectious (environmental)
- infectious
Self (autologous) antigens
failure of self-tolerance
(autoimmunity, autoimmune diseases)
Types of Hypersensitivity Reactions
Type I
Type II
Antibody
mediated
Type III
Type IV
T cell
mediated
Type I
(Immediate hypersensitivity)
(Allergy)
Atopy – inherited propensity of an individual to produce high
levels of IgE to various environmental antigens
Alergen – an antigen that induces immediate hypersensitivity
in atopic people
Charles Richet
1913
Nobel Prize of
Medicine and Physiology
"in recognition of his work on anaphylaxis"
Common allergens
Common allergens
Food allergens (“the big eight”)
The sequence of events
The sequence of events
Type I
hypersensitivity
Biochemical events in mast cell activation
High level IgE production is
determined by:
• Genetic factors
(MHC II, cytokines, cytokine receptors...)
• Nature of allergen
(mass, glycosylation, charge, stability)
• Environmental factors
(exposure to microbes, polution, smoking...)
Clinical manifestasions
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Alergic conjuctivitis
Alergic rhinitis (hay fever)
Alergic (bronchial) asthma
Hives (Urticaria)
Atopic dermatitis
Food allergy
Anaphylaxis (systemic)
Testing for type I hypersensitivityin vivo
Skin tests
Prick testing
Intradermal testing
Provokativni testovi
Bronchoprovocative tests (metacholin chloride or alergen)
DBPCFC (Double-Blind Placebo-Controlled Food Challenge)
Prick testing
15 min.
Swelling and redness
Swelling
2mm › negative control – positive
≥ 5mm – clinically relevant
5-10 mm weak sensitivity
10-15 mm moderate sensitivity
› 15 mm strong sensitivity
Testing for type I hypersensitivityin vitro
Total IgE
 nephelometry ...
Alergen specific IgE
 RAST
(RadioAllergoSorbent Test)
 EIA (PHADIA ImmunoCap ...)
Therapy
• Inhibition of mast cell degranulation (cromolyn)
• Blocking of mast cell mediator effects (antihistamines)
• Reduction of inflammation (corticosteroids)
• Bronchial smooth muscle relaxation (phosphodiesterase
inhibitors)
• “Desensitization” – repeated administration of allergen
• Epinephrine - anaphylaxis